Potent, highly specific, irreversible and cell-permeable inhibitor that covalently modifies the catalytic β subunits (chymotrypsin-, trypsin- and caspase-like activities) of the proteasome. Lactacystin is hydrolyzed in aqueous solutions to a clasto-lactacystin β-lactone intermediate which is the active inhibitory species that reacts with the proteasome.